Shedding of Ann Arbor strain live attenuated influenza vaccine virus in children 6-59 months of age

Vaccine. 2011 Jun 10;29(26):4322-7. doi: 10.1016/j.vaccine.2011.04.022. Epub 2011 Apr 20.


Background: A trivalent, Ann Arbor strain, live attenuated influenza vaccine (LAIV) is approved for use in children 24 months of age and older in a number of countries. The incidence, duration, and other parameters of viral shedding after vaccination with LAIV have not been fully described in children ≤ 5 years of age.

Methods: An open-label, single-arm, multicenter, phase 2 study assessed viral shedding and safety in 200 children 6-59 months of age after a single, intranasal dose of LAIV in 2006. Participants were enrolled into 2 age groups: 6-23 months (n=100) and 24-59 months (n=100) of age. Viral shedding, reactogenicity, and adverse events were assessed for 28 days postvaccination. Serious adverse events and significant new medical conditions were monitored for 180 days postvaccination.

Results: Viral shedding was detected by culture in 79% (95% CI, 73-84) of vaccine recipients and occurred more frequently in children 6-23 months of age (89%) compared with children 24-59 months of age (69%). In total, 157 subjects shed vaccine, which was confirmed by RT-PCR as A/H1N1 for 128 subjects, A/H3N2 for 72 subjects, and B for 74 subjects. The incidence of shedding was highest on day 2 (59% in the 6-23 month age group; 41% in the 24-59 month age group) and most shedding occurred 1-11 days postvaccination; shedding after 11 days was infrequent and occurred almost exclusively in children 6-23 months of age. Mean titers of shed vaccine virus peaked on day 2 and were generally <10(3.0) median tissue culture infective dose/mL for both groups. Reactogenicity events peaked on day 2; runny/stuffy nose was reported most frequently (63% of all subjects).

Conclusion: Most children 6-59 months of age vaccinated with Ann Arbor strain LAIV shed ≥ 1 vaccine virus within 11 days of vaccination. Shedding was less common in children 24-59 months of age, a population for whom LAIV is approved for use. Titers of shed vaccine were low, which may explain why secondary transmission of LAIV was observed very infrequently in a previous controlled study conducted with young children in a daycare setting.

Trial registration: NCT00344305.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H1N1 Subtype / isolation & purification
  • Influenza A Virus, H1N1 Subtype / physiology
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / isolation & purification
  • Influenza A Virus, H3N2 Subtype / physiology
  • Influenza A virus / immunology
  • Influenza A virus / isolation & purification
  • Influenza A virus / physiology*
  • Influenza B virus / immunology
  • Influenza B virus / isolation & purification
  • Influenza B virus / physiology*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Male
  • Treatment Outcome
  • Vaccination
  • Vaccines, Attenuated / administration & dosage*
  • Vaccines, Attenuated / immunology
  • Virus Shedding*


  • Influenza Vaccines
  • Vaccines, Attenuated

Associated data